Effects of calcium and its antagonists on the canine mesenteric circulation.
We studied circulatory and metabolic responses of the intestinal circulation to intraarterial infusions of solutions containing calcium chloride or calcium antagonists in anesthetized dogs. Measurements included blood flow to the terminal ileum, arteriovenous oxygen content difference, distribution of radiolabeled microspheres to the mucosal-submucosal compartment and intraluminal pressure. Calculated parameters included oxygen consumption and fractional mucosal-submucosal blood flow. Both calcium antagonists, nifedipine and diltiazem, increased intestinal blood flow, mainly to the mucosa-submucosa, depressed intestinal motility, and did not change oxygen consumption. Thus, both agents appear to act mainly on resistance vessels without increasing the nutrient circulation. Calcium chloride (1.0-500.0 microgram/kg per min) had a mild constrictor effect; at a dose of 1000.0 microgram/kg per min, calcium chloride became a dilator agent in the mesenteric circulation. The dilator effect of the highest dose of calcium was reversed by digoxin, suggesting the involvement of Na+,K+-ATPase. Nifedipine completely blocked calcium-induced constriction of the intestinal circulation and partly inhibited norepinephrine-induced constriction. Studies on isolated mesenteric arterial smooth muscle revealed that nifedipine relaxed KCl-contracted strips in the presence of external calcium and relaxed norepinephrine-contracted strips in both the presence and absence of external calcium. These in vitro findings suggest that calcium antagonists interfere with the release of calcium from intracellular sites as well as with the slow inward current of calcium.
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002122:Calcium Chloride / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D009119:Muscle Contraction; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D012492:Salts; D013152:Splanchnic Circulation
D012492:Salts; D004533:Egtazic Acid; D004077:Digoxin; D004110:Diltiazem; D009543:Nifedipine; D002122:Calcium Chloride; D002118:Calcium; D009638:Norepinephrine